tbuckley/cabot-search huggingface dataset:
Adverse Drug Reactions in Hospitalized Patients
Authors: Kenneth Fremont-Smith
Journal: JAMA (1998)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Highlights of This Issue
Journal: Clinical Cancer Research (2015)

Ben Tanfous and colleagues analyzed an association between asparaginase pathway genes and E.coli asparaginase related complications in child acute lymphoblastic leukemia. Triple repeat allele of asparagine synthetase (ASNS) gene increased several fold the risk of allergies and pancreatitis. Particular ASNS haplotype had, in contrast, protective effect. Deeper insight into the association observed was assessed through analysis of additional polymorphisms in the ASNS gene and their influence on asparaginse sensitivity in vitro. The authors provided information on biomarkers that may possibly monitor complications associated with asparaginase treatment.The CC chemokine receptor 4 (CCR4) is expressed on many T-cell subsets. Mogamulizumab, a defucosylated anti-CCR4 antibody, can induce antibody-dependent cellular cytotoxicity against CCR4+ malignant T cells in cutaneous T-cell lymphoma (CTCL). Ni and colleagues completed a translational study accompanying to a phase I/II trial to determine the effect of mogamulizumab on different T-cell subsets in CTCL patients. Following one course of therapy, mogamulizumab reduces CCR4+ malignant T cells in blood and skin, also eliminates CCR4+ regulatory T cells, but has limited effect on CD8+ T cells. Besides improving clinical management in CTCL, mogamulizumab may have potentials in treating other cancer patients with immunosuppressive mechanisms involving regulatory T cells.The heterogeneous composition of cancers results in variability of therapeutic response to clinical regimens. Chang and colleagues describe an innovative approach to individualize treatments by using a mechanism-associated PET imaging tracer (18F-FAZA) to closely monitor the efficacy of a novel anticancer drug, BAY 87-2243. By assessing the degree to which the drug affects tracer uptake, one can then judge the effectiveness of the drug and thereby quickly adjust dosage. Tracer uptake can also be used to assess staging of the disease as well as evolution of resistance with treatment before significant reduction in tumor volume.Gefitinib, an EGFR tyrosine kinase inhibitor, has led to a great advance in the treatment of NSCLC with EGFR activating mutation; however, acquired resistance is inevitable. Lin and colleagues first disclosed that DUSP1 downregulation is responsible for gefitinib-acquired resistance. HDAC1 inhibition could induce DUSP1 upregulation to restore gefitinib sensitivity in vitro and in preclinical models. Clinically, decreased DUSP1 was correlated with the emergence of acquired resistance and could serve as a predictive biomarker. Therefore, this study provides not only mechanistic insights into gefitinib-acquired resistance but also an effective approach to overcome it.
Highlights of This Issue
Journal: Clinical Cancer Research (2014)

LHRH receptors are expressed on the cell membrane of prostate cancer cells and may provide novel therapeutic targets in patients with treatment refractory prostate cancer. Liu and colleagues report a phase I trial of AEZS-108, a hybrid molecule that couples an LHRH agonist with doxorubicin. The agent was well tolerated in heavily pretreated patients and showed early signs of efficacy. In addition, the autofluorescent properties of doxorubicin permitted visualization of internalization in circulating tumor cells, highlighting a potential pharmacodynamic predictive marker for future use of this drug.Demcizumab, a humanized antibody targets the Notch pathway component delta-like ligand 4 (DLL4). Notch plays a critical role in the maintenance of tumor cells with stem-cell properties. Smith and colleagues conducted this phase I trial of demcizumab in patients with advanced solid tumors. Downregulation of stem cell-related genes and upregulation of vascular/endothelial genes occurred starting at 2.5 mg/kg every other week. Patients treated at 10 mg/kg every other week had disease stabilization and decreases in tumor size and prolonged exposure resulting in the emergence of delayed cardiac toxicity. Demcizumab shows promising anticancer activity and novel toxicities warranting further investigation.Resistance to the EGFR inhibitors cetuximab or panitumumab in colorectal cancer is caused by the emergence of mutations in the RAS pathway. In biopsies from relapsed patients, however, only a fraction of cells carry RAS mutations, suggesting that wild-type cells can also survive the treatment. Hobor and colleagues report that sensitive cells grow in the presence of cetuximab when in the company of their resistant derivatives. They find that cells bearing acquired RAS mutations over-secrete the EGFR ligands TGFα and amphiregulin, which protect the surrounding wild-type cells. This paracrine network can be targeted to increase the efficacy of anti-EGFR therapies.Genotype-directed therapy using kinase inhibitors is the standard of care for subsets of lung cancer patients whose tumors harbor oncogenic alterations. These alterations are more frequently detected in never smokers with non-small cell lung cancer, but not all patients harbor a known oncogenic alteration. To identify additional targetable alterations, Capelletti and colleagues screened 576 adenocarcinomas from never smokers. They identified FGFR3-TACC3 rearrangements in three patients of this cohort. In vitro experiments demonstrated that this alteration is oncogenic and sensitive to pan-FGFR inhibitors. These findings suggest that patients harboring FGFR3-TACC3 rearrangement should be considered for clinical trials featuring FGFR inhibitors.
Long-term Cholesterol-Lowering Effects of 4 Fat-Restricted Diets in Hypercholesterolemic and Combined Hyperlipidemic Men
Authors: Robert H. Knopp
Journal: JAMA (1997)

<h3>Context.</h3> —The long-term effect of aggressively vs moderately fat-restricted diets has not been studied extensively in free-living subjects with different types of hyperlipidemia. <h3>Objective.</h3> —To compare the cholesterol-lowering effects of 4 levels of dietary fat intake restriction after 1 year. <h3>Desing.</h3> —Randomized, parallel, comparison trial. <h3>Setting.</h3> —Male employees of a large industry. <h3>Participants.</h3> —A total of 444 men had low-density lipoprotein cholesterol (LDLC) levels above the 75th age-specific percentile. Subjects with triglyceride (TG) levels less than the 75th age-specific percentile were defined as hypercholesterolemic (HC) and those with TG levels at or above the 75th age-specific percentile were defined as combined hyperlipidemic (CHL). <h3>Interventions.</h3> —Hypercholesterolemic subjects were randomized to diets 1, 2, 3, and 4 taught to contain 30%, 26%, 22%, and 18% fat, and the CHL subjects were randomized to diets 1,2, and 3. All 4 diets were taught to subjects and spouses or partners in 8 weekly 2-hour classes. <h3>Main Outcome Measures.</h3> —Plasma lipoprotein levels after 1 year. <h3>Results.</h3> —Fat intake after 1 year declined from a mean of 34% to 36% of energy to 27%, 26%, 25%, and 22% in the 4 HC diet groups and 28%, 26%, and 25% in the 3 CHL diet groups. Mean±SD percent LDL-C reductions were 5.3%±16.2%, 13.4%±12.6%, 8.4%±11.2%, and 13.0%±15.7% in the HC diet groups and 7.0%±16.2%, 2.8%±15.8%, and 4.6%±13.5% in the CHL diet groups (<i>P</i>&lt;.01 in all but 1 instance). Apoprotein B levels decreased 8.6%, 10.7%, 4.3%, and 5.3% in the HC groups and 14.6%, 11.4%, and 9.9% in the CHL groups (<i>P</i>&lt;.05-.01 in each instance). Triglyceride levels increased significantly in subjects following HC diets 3 and 4, 21.7% and 38.7% (<i>P</i>&lt;.05 and.01), but not in any CHL subjects. High-density lipoprotein cholesterol decreased 2.8% and 3.2% in subjects on HC diets 3 and 4, respectively (<i>P</i>&lt;.05 in both cases). <h3>Conclusions.</h3> —After 1 year, moderate restriction of dietary fat intake attains meaningful and sustained LDL-C reductions in HC subjects and apoprotein B reductions in both HC and CHL subjects. More extreme restriction of fat intake offers little further advantage in HC or CHL subjects and potentially undesirable effects in HC subjects.
Brachial and femoral artery blood flow in cirrhosis: Relationship to kidney dysfunction
Authors: Albert Maroto, Pere Ginés, Vicente Arroyo, Angels Ginés, Joan Saló, Joan Clária, Wladimiro Jiménez, Concepció Bru, Francisca Rivera, Joan Rodés
Journal: Hepatology (1993)

Brachial artery and common femoral artery blood flows and cardiac output were measured with duplex-Doppler ultrasonography in 12 normal subjects, 12 patients with compensated cirrhosis and 35 patients with cirrhosis and ascites (8 with functional kidney failure). The aim of this study was to investigate whether arteriolar vasodilation in these vascular territories contributes to hyperdynamic circulation in cirrhosis. Cardiac output was significantly increased and systemic vascular resistance significantly reduced in the three groups of cirrhotic patients. We found no significant differences between normal subjects and compensated cirrhotic patients in brachial artery (55 ± 7 vs. 57 ± 7 ml/min) and femoral artery (353 ± 20 vs. 310 ± 25 ml/min) blood flow. Nonazotemic cirrhotic patients with ascites showed significantly lower (p &lt; 0.05) brachial artery blood flow (40 ± 3 ml/min) than healthy subjects and compensated patients. Femoral artery blood flow (327 ± 25 ml/min), however, was not significantly different. Brachial artery (25 ± 3 ml/min) and femoral artery (213 ± 22 ml/min) blood flows were markedly reduced in the patients with kidney failure (p &lt; 0.05 with respect to the other three groups). Glomerular filtration rate correlated directly with brachial (r = 0.74, p = 0.0001) and femoral (r = 0.52, p = 0.03) artery blood flow in the cirrhotic patients. These results indicate that the arteriolar vasodilation causing hyperdynamic circulation in cirrhosis does not take place in the brachial and femoral vascular territories. (Hepatology 1993;17:788-793.)
Ruptured Chordae Tendineae
Journal: New England Journal of Medicine (1959)

s hypothesis, which is also Poskanzer's,' is that early exposure to infec- ton in low risk areas prevents the later development of M.S.If this were true, how- ever, the "unexposed" immigrants should show a much higher attack rate than is found in their native lands, which seems not to be the case in Australia, Dutch Antilles, Israel, or South Africa.Further, the native-born English-speaking South Africans, as well as the Israelis, are recent arrivals, and from neither land do the current prevalence studies indicate any appreciable rate of M.S. in the parents of the subjects.Thus the evidence suggests that M.S. is " caught" in the high risk areas and brought by the migrants in a latent form into these low risk regions which provide such an invaluable human laboratory for M.S.What is the latent period can perhaps be better defined from the points raised here with the data available to Dr.
Chest pain; heart or gullet?
Authors: J R Bennett
Journal: BMJ (1983)

Thank you for your interest in spreading the word about The BMJ.NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address. Username * Your Email * Send To * You are going to email the following Chest pain; heart or gullet? Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Yersinia Hepatic Abscesses Subsequent to Long-term Iron Therapy
Authors: Peter M. Leighton
Journal: JAMA (1987)

A 71-year-old woman who had been receiving iron injections for at least ten years was admitted to the Dr Everett Chalmers Hospital, Fredericton, New Brunswick. The initial diagnosis was metastatic tumors in the liver, but after further evaluation, the initial diagnosis was corrected to multiple hepatic abscesses due to<i>Yersinia enterocolitica</i>. The liver biopsy showed abundant iron deposition. With the appropriate antibiotic treatment, the patient recovered. (<i>JAMA</i>1987;257:964-965)
Early Definitive Treatment of Vascular Injuries in the Vietnam Conflict
Authors: James G. Chandler
Journal: JAMA (1967)

One hundred twenty-six vascular repairs in 118 Vietnam battle casualties resulted in a 5.1% mortality and a 19.8% amputation rate. These injuries differed from those seen in previous armed conflicts primarily because of the extremely short time between wounding and treatment typical of the medical evacuation system in South Vietnam. The overall severity of these cases is best attested by their average blood transfusion requirement of 5,800 ml. Particular consideration is directed to the specifics of perioperative care, the technical features of vessel reconstruction, and the value of certain ancillary measures. The amputated cases are reviewed for remedial errors and their potential for improved limb salvage.
Hazards Associated With Diaper Changing
Authors: Mary A. McCormick
Journal: JAMA (1982)

The incidence of exposure to poisons occurring in children during diaper changing was recorded during a three-month period. There were 138 cases, with 79% between the ages of 7 to 18 months; 42% of the poisonings occurred between 5 PM and 9 PM. Powders accounted for 47% of the exposures. Symptoms were mild and occurred most often with powders. During diaper changing, children are at increased risk of poisoning. (<i>JAMA</i>1982;248:2159-2160)
Dual Pathways for Nuclear Factor κB Activation by Angiotensin II in Vascular Smooth Muscle
Authors: Liping Zhang, Jizhong Cheng, Yewei Ma, Walter Thomas, Jiqiang Zhang, Jie Du
Journal: Circulation Research (2005)

Activation of nuclear factor (NF)-κB by angiotensin II (Ang II) plays an essential role in stimulating expression of vascular adhesion molecules, which are essential for vascular inflammation. We report that Ang II activates NF-κB by phosphorylating its p65 subunit via a pathway mediated partially by ribosomal S6 kinase (RSK). In investigating other pathway(s) that may be involved, we found that the ability of Ang II to activate NF-κB in mouse embryonic fibroblast is suppressed (&amp;70%) either by deletion of IκB Kinase (IKK) or by inhibiting or knocking down IKK in vascular smooth muscle cells using a dominant-negative IKK adenovirus or small interference RNA to IKKβ. Thus, Ang II also stimulates NF-κB via IKK. In vitro, we found that Ang II stimulates IKK to phosphorylate myelin basic protein and the p65 subunit of NF-κB. The mechanism by which Ang II activates IKK is to increase phosphorylation of IKKβ in its activation loop (Ser181) rather than IκB phosphorylation. Inhibiting both the RSK and IKK pathways completely blocks the Ang II–induced p65 phosphorylation and NF-κB activation. These 2 pathways are independent: inhibiting IKK does not block Ang II–induced phosphorylation of RSK, whereas inhibiting mitogen-activated protein kinase 1 does not affect phosphorylation of IKK. Finally, we found that Ang II can induce expression of vascular adhesion molecules by 2 pathways; both IKK and RSK lead to phosphorylation of the p65 subunit of NF-κB to increase vascular cell adhesion molecule-1 transcription. The 2 pathways are functionally important because inhibiting IKK and RSK in vascular smooth muscle cells blocks Ang II–induced expression of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 to limit vascular inflammation.
Oral Cancer and Mouthwash
Authors: Blot, William J., Winn, Deborah M., Fraumeni, Joseph F.
Journal: JNCI Journal of the National Cancer Institute (1983)

Journal Article Oral Cancer and Mouthwash Get access William J. Blot, William J. Blot 3 3Address reprint requests to Dr. Blot, Landow Building, Room 3C09, National Institutes of Health, Bethesda, Md. 20205. Search for other works by this author on: Oxford Academic PubMed Google Scholar Deborah M. Winn, Deborah M. Winn Search for other works by this author on: Oxford Academic PubMed Google Scholar Joseph F. Fraumeni, Jr. Joseph F. Fraumeni, Jr. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 70, Issue 2, February 1983, Pages 251–253, https://doi.org/10.1093/jnci/70.2.251 Published: 01 February 1983 Article history Received: 03 July 1982 Accepted: 19 October 1982 Published: 01 February 1983
Cultivation of Rat Bone Marrow. I. Preliminary Studies and Some Effects of Hemolyzed Blood as Nutrient<xref ref-type="fn" rid="FN1">2</xref>
Authors: Helen J. Morton, Richard J. Isaacs
Journal: JNCI Journal of the National Cancer Institute (1967)

Some techniques for the study of erythropoiesis in vitro were examined. The beneficial erfect of decreased temperature of incubation was confirmed. Homologous serum was superior to heterologous serum, but this effect depended on the concentration, source, and hemoglobin content of the serum used. When added to serum, the products of hemolyzed red cells had a marked beneficial effect. This may be related to nutritional requirements. Using high concentrations of serum (75% or more) prevented fibroblast overgrowth of the culture. Underthe optimum conditions, e secend wave of reticulocyte production could be. produced by removal of most mature erythrocytes at 5 days. Small, but significant, numbers of reticulocytes and erythrocytes were produced For as long as 10 days in vitro.
Smoking among secondary schoolchildren
Authors: A. Charlton, D. White
Journal: BMJ (1995)

that the total dosage of antimalarial drugs is related to toxicity,' it may well be correct, as suggested in Mackenzie's paper, that the true relation is with the daily dose, based on lean body mass.There is an important inference to be drawn from Mackenzie's work-that the normally recom- mended dosages may well be too high in either very slim people or very fat people.
Protein Kinase Cα, but Not PKCβ or PKCγ, Regulates Contractility and Heart Failure Susceptibility
Authors: Qinghang Liu, Xiongwen Chen, Scott M. MacDonnell, Evangelia G. Kranias, John N. Lorenz, Michael Leitges, Steven R. Houser, Jeffery D. Molkentin
Journal: Circulation Research (2009)

Protein kinase (PK)Cα, PKCβ, and PKCγ comprise the conventional PKC isoform subfamily, which is thought to regulate cardiac disease responsiveness. Indeed, mice lacking the gene for PKC α show enhanced cardiac contractility and reduced susceptibility to heart failure. Recent data also suggest that inhibition of conventional PKC isoforms with Ro-32-0432 or Ro-31-8220 enhances heart function and antagonizes failure, although the isoform responsible for these effects is unknown. Here, we investigated mice lacking PKC α, PKC β, and PKC γ for effects on cardiac contractility and heart failure susceptibility. PKC α −/− mice, but not PKC βγ −/− mice, showed increased cardiac contractility, myocyte cellular contractility, Ca 2+ transients, and sarcoplasmic reticulum Ca 2+ load. PKCα −/− mice were less susceptible to heart failure following long-term pressure-overload stimulation or 4 weeks after myocardial infarction injury, whereas PKC βγ −/− mice showed more severe failure. Infusion of ruboxistaurin (LY333531), an orally available PKCα/β/γ inhibitor, increased cardiac contractility in wild-type and PKC βγ −/− mice, but not in PKC α −/− mice. More importantly, ruboxistaurin prevented death in wild-type mice throughout 10 weeks of pressure-overload stimulation, reduced ventricular dilation, enhanced ventricular performance, reduced fibrosis, and reduced pulmonary edema comparable to or better than metoprolol treatment. Ruboxistaurin was also administered to PKC βγ −/− mice subjected to pressure overload, resulting in less death and heart failure, implicating PKCα as the primary target of this drug in mitigating heart disease. As an aside, PKC αβγ triple-null mice showed no defect in cardiac hypertrophy following pressure-overload stimulation. In conclusion, PKCα functions distinctly from PKCβ and PKCγ in regulating cardiac contractility and heart failure, and broad-acting PKC inhibitors such as ruboxistaurin could represent a novel therapeutic approach in treating human heart failure.
Emergency Treatment of Cardiac Arrhythmias
Authors: Don M. Benson
Journal: JAMA (1971)

<h3>To the Editor.—</h3> Escher and Fruman in Table 1 of their article "Emergency Treatment of Cardiac Arrhythmias: Emphasis on Use of Electrical Pacing," (<b>214</b>:2028-2034, 1970) list intracardiac injection as the preferred drug administration route in cardiac arrest emergencies. While the drama and romance of plunging instruments into the chest wall may intrigue physicians and bystanders, rapidly fatal complications such as tension pneumothorax and pericardial tamponade may result. Interruption of cardiopulmonary resuscitation in excess of the accepted maximum of 5 seconds may be required before blind stabs through the chest wall locate a blood filled viscus. When an organ from which blood can be aspirated is finally located and the cardiotonic is injected, the operator is obliged to withdraw the needle before external cardiac compression is resumed. A continuous infusion cannot be started. Less hazardous and equally effective drug administration routes are available. Redding et al (<i>Anesth Anal</i><b>46</b>:253-258,
Coronary Reperfusion: Medical, Surgical, or Not at All?
Authors: K. Lance Gould
Journal: JAMA (1982)

In this issue of The Journal (p 1325), Phillips et al report improved ventricular function and survival in patients undergoing immediate bypass surgery for acute myocardial infarction, findings similar to their earlier observations in 1979.<sup>1</sup>Berg<sup>2</sup>and DeWood et al<sup>3</sup>from Spokane, Wash, initially reported improved survival in patients who had undergone coronary bypass surgery as compared with medically treated patients with acute myocardial infarction. These articles demonstrate both the promise and the problems of innovative, aggressive intervention to reperfuse jeopardized myocardium, demonstrated by most,<sup>4-7</sup>but not all,<sup>8-10</sup>experimental studies to be beneficial. On the positive side, Phillips et al have set aside arbitrary assumptions about a fixed, maximum duration of chest pain beyond which salvage is considered infeasible. Their decision for surgical intervention depended on clinical evidence of ongoing ischemia that indicated remaining viable myocardium as compared with depending on rigid time periods based